One more bit of evidence burying the ex-hypothesis that vaccines cause autism

May I just say something again? (Actually, it’s my blog; so I’ll say it if I want to regardless of whether you want me to or not.) You know that “hypothesis” that vaccines cause autism, the one that has been at the core of the modern antivaccine movement over the last 15 years or so? Well, it’s not pining for the fjords, if you know what I mean. No it’s not pinin’! It’s passed on! This “hypothesis” is no more! It has ceased to be! It’s expired and gone to meet it’s maker! (Well, actually, since one of its makers, Andrew Wakefield, is still around, I’m not sure what in practice that actually means.) It’s a stiff! Bereft of life, it rests in peace! If antivaccinationists hadn’t nailed it to the perch it’d be pushing up the daisies! Its metabolic processes are now ‘istory! It’s off the twig! It’s kicked the bucket, It’s shuffled off this mortal coil, run down the curtain and joined the bleedin’ choir invisible!! THIS IS AN EX-HYPOTHESIS!!

Sorry, but I just have to do that every so often because I like both Monty Python and rhetorically beating on antivaccinationists, and I just had a nice excuse to indulge my passion for both.
Actually, this bit of fun was delayed because there was a problem over the weekend. Sometimes it’s a good problem to have; sometimes not so good. As it turned out, there were just too many things out there that I wanted to blog about. So I picked and I chose, and ended up writing about Mike Adams’ ham-fisted attempt to use legal thuggery to silence a critic, as well as another topic at my not-so-super-secret other blog. Now that that satisfying bit of blogging is taken care of, it’s time for what will be another satisfying bit of blogging. I’m referring to a large meta-analysis that demonstrates once again something that regular readers of this blog already know. Specifically, it comes to the not-unexpected conclusion that vaccines are not associated with autism. In fact, that’s the title of the meta-analysis by Taylor et al, Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies. It’s an article in press, but can be found here.

Let’s take a step back. The results of this study are singularly unsurprising. The reason is, well, because it’s a meta-analysis. As I’ve discussed time and time again, the overwhelming preponderance of evidence does not support the now discredited idea that there is a correlation between vaccines and autism (or, for that matter, between the mercury-containing preservative thimerosal that used to be in childhood vaccines). Taken in its totality, the evidence is most consistent with the conclusion that there is no association between vaccines and autism, so much so that if there is a correlation it would have to be incredibly small to be less than the expected noise inherent in large epidemiological studies.

I’m going to cut to the chase (I know, I know, uncharacteristic of me) and list the findings first. Then I’ll discuss a bit about the methods:

Five cohort studies involving 1,256,407 children, and five case-control studies involving 9,920 children were included in this analysis. The cohort data revealed no relationship between vaccination and autism (OR: 0.99; 95% CI: 0.92 to 1.06) or ASD (OR: 0.91; 95% CI: 0.68 to 1.20), or MMR (OR: 0.84; 95% CI: 0.70 to 1.01), or thimerosal (OR: 1.00; 95% CI: 0.77 to 1.31), or mercury (Hg) (OR: 1.00; 95% CI: 0.93 to 1.07). Similarly the case-control data found no evidence for increased risk of developing autism or ASD following MMR, Hg, or thimerosal exposure when grouped by condition (OR: 0.90, 95% CI: 0.83 to 0.98; p = 0.02) or grouped by exposure type (OR: 0.85, 95% CI: 0.76 to 0.95; p = 0.01). Findings of this meta-analysis suggest that vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines (thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder.

In other words, in a group of studies that encompass nearly 1.3 million children, there was no hint of an association between vaccination and autism or between vaccination and autism spectrum disorder (ASD) and no relationship between mercury exposure in vaccines through thimerosal-containing vaccines and autism or ASD. Perhaps most shocking to me, the authors assert (and I have no reason to doubt) that this is the first quantitative pooling of data in a meta-analysis to look at the question of whether there is a correlation between vaccines and autism. This is an omission in the medical literature that is hard to believe.

The authors note that there have been twelve systematic reviews of the literature covering the relationship between vaccines and autism and that only one of them concluded that there was a correlation between the two. Can you guess who wrote it? Yes, it was that infamous turd of a review by Helen V. Ratajczak published in 2011 and trumpeted far and wide by the antivaccine movement. Let’s just put it this way. I was rather shocked that the authors even bothered to include this massive bit of antivaccine pseudoscience. Remember, this was the paper in which Ratajczak claimed that human DNA from vaccines was taken up in human brain cells in a form that could produce foreign proteins and provoke autoimmunity. I kid you not. When that article came out I couldn’t resist producing one of my characteristically logorrheic deconstructions that demonstrated exactly why her article was a proverbial steaming pile of fetid dingo’s kidneys. I suppose the authors had to mention her article, but it’s so full of pseudoscience, misrepresentation of science, and twisting of evidence that a good case could be made for not including it and saying that eleven out of eleven systematic reviews conclude that there is no relationship between vaccination and autism.

Of course, a meta-analysis is not a new study. It’s a study that aggregates existing studies, and, as I’ve often said, the danger of meta-analysis is what I like to call the “garbage in garbage out” phenomenon. In other words, aggregating a bunch of bad studies won’t magically turn them into gold, like some alchemist. So what about the studies included? Fortunately, they’re all decent studies, basically the big names that get cited time and time again, studies such as Price et al (for example). They also excluded studies that used the Vaccine Adverse Events Reporting System (VAERS) as their data source as described:

Papers that recruited their cohort of participants solely from the Vaccine Adverse Event Reporting System (VAERS) in the United States were not included due to its many limitations and high risk of bias including unverified reports, underreporting, inconsistent data quality, absence of an unvaccinated control group and many reports being filed in connection with litigation [5] and [6].

Not surprisingly, antivaccinationists are not pleased with the publication of this particular meta-analysis. Even though it’s not the be-all and end-all of evidence with respect to vaccines and autism, it is yet another piece of evidence demonstrating that vaccines are not correlated with autism. True, it’s a particularly powerful piece of evidence, but just a piece nonetheless. I’m also enormously puzzled why the editors of Vaccine allowed the authors to publish this “epilogue” from Guy Eslick, the senior author:

As an epidemiologist I believe the data that is presented in this meta-analysis. However, as a parent of three children I have some understanding of the fears associated with reactions and effects of vaccines. My first two children have had febrile seizures after routine vaccinations, one of them a serious event. These events did not stop me from vaccinating my third child, however, I did take some proactive measures to reduce the risk of similar adverse effects. I vaccinated my child in the morning so that we were aware if any early adverse reaction during the day and I also gave my child a dose of paracetamol 30 min before the vaccination was given to reduce any fever that might develop after the injection. As a parent I know my children better than anyone and I equate their seizures to the effects of the vaccination by increasing their body temperature. For parents who do notice a significant change in their child’s cognitive function and behaviour after a vaccination I encourage you to report these events immediately to your family physician and to the ‘Vaccine Adverse Event Reporting System’.

To be honest, I don’t recall ever seeing anything like this in a scientific paper before, and including such commentary in the paper itself is unscientific and unnecessary. I realize that the authors probably wanted to demonstrate that they understand parental fears, but I would submit that the discussion of a scientific article reporting peer-reviewed results of a meta-analysis of the literature examining the question of whether vaccination can cause autism. Such an anecdote might be appropriate in an accompanying editorial or in a commentary, but it’s completely inappropriate for an actual scientific studie or meta-analysis.

That curious misstep aside, this appears to be a well-designed meta-analysis. One could argue that it’s unnecessary because it doesn’t tell us anything we don’t already know, but doing meta-analyses instead of systematic reviews seems to be more in fashion these days; so I’m content to go with it. Not that it will ever persuade antivaccinationists that vaccines are safe and effective, but it’s useful as another bit of dirt to put on the grave of the ex-hypothesis that vaccines cause autism.

Isn’t it obvious? The authors of the study are thralls of Big Pharma, toiling hard and finding small, disreputable studies dolne by researchers with deep seated conflicts of interest, just to produce this travesty ot meta-analysis, which is another obvious lie of The Man who wants to turn everyone in to vaccine zombies.

And whats the bet that most of the anti-vaxxers will remain silent – the actual article flying high over their heads – even despite their totes awesum research skillz – until their chosen guru “interprets” it for them.

And whats the bet that most of the anti-vaxxers will remain silent – the actual article flying high over their heads – even despite their totes awesum research skillz – until their chosen guru “interprets” it for them.

janerella, you would lose that bet. Autism Speaks has a post up about that meta analysis and the anti-vaxxers have been posting a slew of comments. 🙂

I’m not sure if I agree with your view of of the author’s comment. It appears to me to strengthen his findings. He is basically saying that he was willing to expect that his meta-analysis would find grounds to suspect a problem. In other words, this was his bias.

Ah yes, but, having just perused those comments – no one is actually reading and specifically picking apart any of the epidemiology/statistics in the actual article, despite everyone proclaiming regularly their equal-to-scientists’ ability to interpret research. They’re just flailing about with the usual tropes, and I highly doubt any of them have even read the actual article in the 10 hours or so since you posted it.

Jeff1971: I agree with Orac that the senior author’s personal concerns about vaccinating his children because of a family history of post-vaccine febrile seizures, is not appropriate. That comment might be appropriate if he was being interviewed about his study.

janarella, none of those anti-vaxxers has the skill set to refute the meta analysis study’s findings.

You know…FINALLY! Finally we can put to rest something that was PUT TO REST YEARS AGO. And wasn’t even BIOLOGICALLY PLAUSIBLE.

You know, as much as I hate AS, and hate AS dancing around the non-issue in their official statement re: vaccines, at least they posted the article. And you gotta love how many people are now saying AS is in the pocket of Big Pharma. I hate them, but even I don’t think that.

There is a list of “questions” that have been posted up at AoA that they want Dr. Insel to answer (I love the tagline – questions from the Autism community) – they really get to the heart of the crazy belief system they’ve constructed for themselves over there…..

Jeff1971
We cannot know what the thinking was behind the author’s decision to include a personal anecdote in the paper. Perhaps the intended message was that adverse events like febrile seizures are a price well worth accepting for a treatment which protects against potential events of a far more serious nature. Was the intention to point parents with children with similar histories to the author’s, to follow their example with their later children’s vaccinations?
Only the author knows, but I disapprove whatever the thinking was for setting such a precedent.

high risk of bias including unverified reports, underreporting, inconsistent data quality, absence of an unvaccinated control group and many reports being filed in connection with litigation

This thorough takedown of the idea of using VAERS as the sole source of subjects will, I’m sure, be duly noted and duly ignored by the Usual Suspects in the anti-vax community. Instead, they will project claims of bias onto the authors of this study, because “everybody” (at least in the anti-vax community) “knows” that these things happen.

I agree with Orac and others that the authors should not have editorialized here. As we all know, “data” is not the plural of “anecdote”.

I also don’t really like the inclusion of the personal story. Although it’s clear that this author believes in vaccines, the paragraph will undoubtedly be taken out of context- i.e. that the author believes vaccines have very serious side effects. Perhaps that taking something to reduce inflammation is necessary because inflammation from the evil vaccines is driving neurological damage.

Also the “I know my child better than anyone” line just let’s the anti-vaxx movements say the same thing and continue to not believe or not be convinced by the data.

But I think the inclusion probably was more to appeal to non-scientists using an emotional story, instead of just data and reason.

Unfortunately I wasted time reading AoA’s, TMR’s and the Canary Party’s facebook pages. No, they are not happy.

In other news, we learn that:
– autism probably arises mid-term during pregnancy
– research is mostly concerned with genetics
– the sun comes up in the east and sets in the west
that is, amongst most reasonable people which doesn’t include the aforementioned groups.

When my kids (ages 20, 13, and 10) were small, even the MD and nursing staff suggested prophylactic acetaminophen before vaccine administration, for general comfort and fever management.

Is there any reason to be concerned about the effectiveness of their vaccines at this age?

Wonder if it may be in play in some of the pockets of measles outbreaks? It sure seemed to be pretty standard guidance for the 20 yr old’s cohort. I think that it was less emphasized with the younger two, but it’s one of those parental tips and tricks that once encountered (apparently successfully) with one kid, continues with succeeding kids.

Autism Speaks has a post up about that meta analysis and the anti-vaxxers have been posting a slew of comments.

It’s too bad they’re closed, as the “number of unvax would only need to be 100-200 children to confirm that vaccines cause asthma” guy is asserting, given 9.3% childhood prevalence, that the figure for unvaccinated children is less than 1.29%. You’d need 130 unvaccinated children to show zero prevalence at 95% power and confidence.

For 100 unvaccinated with twice as many vaccinated, the largest detectable signal would be a prevalence of 0.1% in the unvaccinated. At 10:1, you can bring that all the way up to 0.121%. To get 0.157%, that’s 100 unvaccinated and 100,347 vaccinated.

Prophylactic acetaminophen administration hasn’t been shown to reduce the risk of febrile seizures, and this widespread and scientifically bankrupt practice has exposed millions of babies to potentially harmful doses of a drug with a very narrow therapeutic index. Furthermore, two recent prospective studies have shown an association between (prenatal) acetaminophen exposure and adverse neurodevelopment. http://bit.ly/1eG2K9uhttp://bit.ly/1nfKz43

Furthermore, two recent prospective studies have shown an association between (prenatal) acetaminophen exposure and adverse neurodevelopmentI must bring up Brandlistuen again because my idée fixe didn’t get enough attention last time.

I just read this @ AoA and think that it expresses their mode of being-in-the-world so precisely:

Ann Dachel scoffs at a report that predicts a 4 times greater likelihood of autism if the father is employed in technical work by saying that it’s garage because that’s exactly what she was told 15 years ago about her son’s autism as her husand was an engineer. ( see STEM & Baron-Cohen)

Masden et al 2002 had Poul Thorsen as a collaborator. Therefore, the study can be easily dismissed as fraudulent because Thorsen was later indicted over theft of grant money from the CDC after the paper had been published. Or so the argument seems to go.

If that doesn’t work it is because the paper was funded by Big Pharma.

When you point out that is not correct, it is because the paper was funded the CDC and you can’t trust the government.

And it needs to be a vaccinated / completely unvaccinated study. And if that could be done with enough statistical power they’d be wanting a vaccinated / completely unvaccinated parents study. And then… etc etc

There was no relationship between vaccination and autism (ok)
There was no relationship between vaccination and ASD (ok)
There was no relationship between vaccination and MMR (??)
There was no relationship between vaccination and thimerosal (??).
There was no relationship between vaccination and mercury (Hg) (??)

The last three consideration are puzzling me.
A relationship between vaccination and MMR? MMR is a vaccination!
I think that it must be “between autism/ASD and MMR”.

@Ander: The last two make some sense, because vaccines no longer contain thimerosal or any other mercury-containing compound. But yes, I suspect they meant autism/ASD and the other factors listed. And item #3 as written makes no sense; it reminds me of a line from a Wayne and Shuster comedy sketch in which one character, a medical researcher, claims to have made a medical breakthrough: he has discovered a link between cigarettes and tobacco.

@ANP – isn’t that same thing that Jake & Hooker tried to push to show that the CDC was covering up information, even though it was nothing more than a preliminary review of preliminary data, which was later refined with better data which disproved the connection?

I have this wonderful vision of two blokes in suits helping him hold the crayons, and saying; “No, you can have a lollipop when you’re finished Brian… Yes, you can go and play with Jacob, but only once this letter’s finished… Now, that’s not how you spell ‘thimerosal’ is it? Come on, you know how to spell that…”

@ Rebecca *snort* I now have a delicious image of Brian Hooker eating paste in my head.

@Lawrence Pretty sure. And it’s old. And wrong. But also old. They really do like the zombie-memes, and ignoring all the other countries not in the CDC’s guideline “jurisdiction” that have found the same thing.

@ANP – isn’t that same thing that Jake & Hooker tried to push to show that the CDC was covering up information

Looks like they are following the lead of Benghazi-obsessed politicians. If there is no sign of the scandal you started investigating, claim “The cover-up is worse than the crime!” and search for a cover-up instead.

If all else fails, you can always claim that “The cover-up was sufficiently extensive to remove all evidence, proving that the original scandal must have been worse than previously suspected, because why else would the conspirators put so much effort into obscuring it?”

For Narad , you have got to admit that we should at least investigate the most common pharmaceutical exposure for pregnant women and children.

Investigate away. You’re the epi. One can postulate mechanisms until the cows come home (I’m not going through the entire list of links that you didn’t bother commenting on to start with), but a convincing signal would help.

This has nothing to do with repeated tries at threadjacking.

Acetaminophen is a topoisomerase poison:
[http://www].nature.com/nature/journal/v501/n7465/full/nature12504.html

You have to get to a NAPQI buildup first, at which point you (1) have rather more pressing issues on your hands and (2) are still looking at the wrong isozyme* as far as the abstract of your reference is concerned.

But hey, whatever, I’m not an expert. I’m sure you wouldn’t simply drop the phrase “topoisomerase poison” as if it were so commonplace as to make these guys look like a right pair of goofy gophers for explaining it.

So, I tell you what: Since you seem to be fond enough of this one to have tossed it out in more than one comment section, have pity and walk me through it in detail.

Previous comment is in moderation thanks to one link too many. Fun fact: if the concern is topoisomerase poisons, Lee Silsby Compounding Pharmacy, sponsors of the Dachel Medial Report, have a real problem on their hands.

NAPQI is only produced when an overdose swamps the usual metabolic breakdown route, if memory serves. I’ve measured more than a few potentially lethal acetaminophen levels in my time, and monitored the liver failure of those that got to the hospital too late for the antidote. Not a good choice for suicide, especially for those poor souls who, to their surprise, wake up alive, change their minds about wanting to die, and then go into hepatic failure a few days later.

I’ve seen patients at the hospital who had ODed on acetaminophen, and to be sure, that is one of the worst ways to die.

Even if they changed their mind, the fact that they attempted suicide would rule them low on the totem pole for a liver transplant. For those who had a change of heart on suicide, that is a tough burden to bear.

novalox,
Reporting an unexpectedly high level when it was early enough to start treatment was one of the few times working in clinical biochemistry that I felt I had really helped to save a life.

I may have related here before that in the early 80s we had to do an ether extraction and look for UV peaks (better than the old whole blood chloroform extraction for barbiturate ODs, which was horrible). That ended when some of my colleages* dug up some soil outside a factory where they made acetaminophen (paracetamol as we call it here), cultured some bacteria that had learned to eat the stuff, and extracted the enzyme they used to do it. Coupled to NAD/NADH and a dye, they produced a kit that takes just a few minutes to get an accurate result. As a young greenhorn I was very impressed, and thought of them every time I used that or a similar kit over the following decades.

I’m impressed that “autismepi” (and, presumably, “epigeneticone”) has been hit-and-run posting this for eight months without figuring out that topoisomerase poisons do the opposite of what he thinks they do.